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Urinary Tract Infection (UTI)

Diagnosis - see Practical.

Asymptomatic carriage related to host factors more than virulence. Most immunodeficiencies not affected by UTI, except neutrophil disorders. Fimbriae adhere, but also assoicated with virulence eg pyelonephritis. Scarring associated with neutrophil exodus and IL8 expression. Knockout IL8 receptor leads to delated neutrophil exodus but accumulation in kidney, in animal model associated with acute pyelonephritis and scarring.

Reflux is a risk factor for renal scarring, but there are many studies showing that scars can develop without reflux, and that many children with reflux (but without infections) do not develop scars. Scars are associated with infection primarily, esp if delayed treatment, and esp with reflux. Cochrane review did not come out strongly in favour of identifying VUR - nine reimplantations would be required to prevent just one febrile UTI, with no reduction at all in the number of children developing any UTI or renal damage. Archives, 2003

What is the risk of longterm damage? Low, given that UTI is common, the occurrence of CRF is rare, and acute pyelonephritis with severe long term complications is also rare. The only large population-based study (n= 1221) found a low risk of hypertension after 16–26 years: only 9% of children with scarred kidneys became hypertensive cf 6% for unscarred. Glomerular filtration rate in later life was normal in both those with and without scarring. Archives of Disease in Childhood 2007;92:357-361

NICE guidance 2007

New NICE guideline 54 (2007) is in response to the finding that scarred kidneys can occur in context of dysplastic kidneys diagnosed antenatally, without any evidence of UTI. Indeed, many scars found in absence of reflux. Suggests:

UTI diagnosis

See NICE 54. Clean catch ideally, pad if clean catch unsuccessful. UTI diagnosis discussed further on Practical page.

• Under 3 months - urgent microscopy.
• 3/12 to 3yrs - arrange microscopy; dipstick is only for where urgent microscopy is not available and low/intermediate risk of serious illness.
• Microscopy interpretation is simply on basis of pyuria pos/neg, bacteria pos/neg.
• Over 3yrs - dipstick is standard.

For ambiguous microscopy or dipstick treat according to clinical signs.

Treatment

Upper tract defined as fever else loin pain/tenderness

Under 3 months get IV treatment. Else 3 days oral treatment if lower tract, 7-10 days oral for upper tract. If oral cannot be used, 2-4 days IV then oral for total of 10 days(!).

Follow up

Atypical UTI defined as: seriously ill, poor urine flow, abdominal/bladder mass, raised creatinine, septicaemia, failure to respond to appropriate antibiotics within 48 hrs, non-E. coli infection

• Under 6/12, OPD USS sufficient if good response to treatment within 48 hours. If atypical or recurrent (defined as 3 lower tract UTIs, else 1 upper tract plus any other), then urgent USS (to look for obstruction or severe reflux - OPD USS within 6 weeks if simply non-E.coli), later OPD DMSA (ie 4-6 months post infection), MCUG.
• 6/12 to 3 yrs: nothing if good response to treatment within 48 hours. If atypical or recurrent, as above but no MCUG unless:
• family history,
• poor flow,
• dilated tract on US,
• non-E coli.
• Over 3yrs: nothing if good response to treatment within 48 hours. If atypical, only needs urgent USS (OPD USS within 6 weeks if simply non-E.coli). If recurrent, do OPD USS and later DMSA.

If another UTI occurs before the DMSA is done, consider doing it sooner (!).

Prophylactic antibiotics for MCUG (1 day before to 1 day after).

Scotland guidelines

Scottish renal group guidelines are more conservative. Same age groups used, and same definition of recurrent, but no reference to atypical infection.

• Under 6/12, USS for all. Pre-discharge if inpatient. If upper tract or recurrent MCUG (urgently if abnormal USS) and DMSA.
• 6-12 to 3yrs: USS for all. Pre-discharge if inpatient. If upper tract or recurrent DMSA.
• Over 3yrs: Nothing unless upper tract or recurrent, who get DMSA.

If USS or DMSA abnormal, do reflux study ie MCUG for pre-continent, DTPA or MAG3 for the continent (and cooperative).

But:

• USS - not much evidence for benefit, esp if normal antenatal scan, rarely changes management even if something minor found, but harmless. If dilatation seen, do MCUG urgently.
• MCUG - like GORD, maybe you see reflux, maybe you don't, so can you rely on it? NB Cost, radiation, discomfort...
• DMSA - acutely, diagnoses pyelonephritis. Then remain positive for up to 6 months after an infection. Late scan diagnoses scars. But if negative during first UTI episode, rarely (NPV 88%) have VUR and never high-grade VUR. J Pediatrics Volume 150, 1 , January 2007, 96-99
• Some would say that you're better off just checking urine promptly in subsequent febrile illnesses - probably obviates need to do any imaging at all. Hoberman A, NEJM 2003;
• Studies do not address whether placebo or nothing is worse than prophylaxis (Cochrane: suggests about 36% reduction in infection, but all 3 studies biased, and most other work has prophylaxis vs surgery). Eg Sweden, only screen if additional risk factor, and v low prevalence of scars. Garin study (Paeds 2006) non placebo controlled, found no protection from recurrent infection with antibiotic prophylaxis (the rate for those with reflux was close to significance but seemed to be cystitis rather than pyelo) - plus the bugs were resistant. The rate of scarring was actually higher in the prophylaxis group.
• Cycling of antibiotic for prophylaxis may be more rational eg every 2-4 weeks

PIDJ 23(12); 2004:1163-1164 (Roberts, Kenneth)

Treatment

Cochrane review concluded that 2-4 day course of oral antibiotic is as effective as a 7-14 day course in the treatment of lower-tract UTIs in children. PMID 12535494 The majority of febrile infants with UTI have nuclear scan evidence of pyelonephritis, suggesting that infants should not receive short course treatment.

Also concluded that for pyelonephritis oral antibiotics are as effective as the combination of parenteral followed by oral antibiotics. Based on:

• Hoberman's RCT children under 2 with fever and UTI (n=300) - oral cefixime for 2 weeks as good as IV: no difference in defervescence, reinfection, scarring at 6 months (and much cheaper!). Severely ill excluded (eg CRT>3sec) - only 3! Funny group though, mean age of 8 months, 90% female, and a low scarring rate (15%). Pediatrics 99 Vol. 104: 79, Hoberman A.
• Montini Multicentre RCT non-inferiority (n=502, 1/12 to 7yrs). Oral co-amoxiclav for 10 days equivalent to ceftriaxone for three days followed by oral in terms of DMSA scars, time to defervescence. BMJ 2007; 335:386-8

Crucial that oral antibiotics are not vomited, of course.

Gauthier et al treated infants and toddlers with febrile UTIs as outpatients using a single daily dose of intravenous gentamicin until the children were afebrile for at least 24 hours, after which oral amoxicillin (!) was given until the urinary culture report was available. Successful in three quarters. Current Opinion in Pediatrics. 18(2):134-8, 2006

1/3 of UTI E coli resistant to trimethoprim, 2/3 if underlying renal abnormality. 61% of women with UTIs and resistant organisms do not reconsult! So should we use community surveillance to guide prescribing rather than individual culture and sensitivity?

UTI prophylaxis did not reduce recurrent infection (n=611). But lower rate (12%) reported than might be expected. Higher resistance rates are seen in recurrent infections, which could be anticipated (JAMA 2007;298;179)

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